1. Platinum Drugs and DNA Repair: Lessons from the NCI Panel and Clinical Correlates.
- Author
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Robert, Jacques, Laurand, Armelle, Meynard, Delphine, and Morvan, Valérie Le
- Abstract
To study the cellular and molecular determinants of sensitivity and resistance to the classical platinum compounds, we have mined the database of the National Cancer Institute, looking for associations between the expression of given proteins belonging to pathways involved in platinum drug processing, and in vitro sensitivity to platinum drugs. Such observations may shed light on the relative importance of different processes involved in platinum drug – induced cell death. For instance, the expression of HMGB1, which targets platinum-DNA adducts and prevents DNA repair, appears to be positively correlated with the cytotoxicity of all the platinum drugs tested. We also determined the effect of several gene polymorphisms of the DNA repair pathways on the in vitro cytotoxicity of platinum compounds. For instance, the asn118asn polymorphism in the ERCC1 gene appears involved in the cytotoxicity of cisplatin and carboplatin, the variant cell lines being significantly less sensitive to these drugs than the wild-type cell lines or the heterozygous ones. In order to achieve better individualisation of platinum drugs prescriptions, the tracks provided by the NCI-60 panel could select the appropriate genes to be explored, at the level of either gene expression or polymorphisms. For instance, the exploration of HMGB1 expression as a predictor of drug response would be warranted. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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